DESIGN OF NOVEL POLYOXOMETALATE-PEPTIDE HYBRID CONJUGATES

The objective of this thesis revolves around two main directions. The first one involves the development of novel POM-peptide hybrids capable of selectively targeting tumor cells by binding to integrins or the GPRP receptor. The initial investigation was aimed to determine if using the EEEE-βA spacer, Ttds spacer, or the Ttds-EEEE-βA spacer is sufficient to prevent Mn Anderson-Evans POM-peptide (DB) interactions, which were shown to hinder peptide's ability to interact with its receptor. Additionally, the impact of covalently binding the cyclic peptide c(RGDfK) to molybdate was explored to assess if the POM affected its ability to target integrin receptors. The reactivity of vanadate hybrids was also thoroughly investigated to identify potential similarities or differences compared to the Mn-Anderson molybdates. The selection of these clusters among various POMs was based on the double negative charge of the anionic core, which differs from the triple negative charge of molybdates. This choice aimed to minimize the cluster's influence on the peptide structure, thus avoiding undesired interactions even without the presence of spacers. The second direction focuses on the creation of POM-peptide hybrids with the potential to target Aβ and inhibit its fibrillation process, thus mitigating the progression of Alzheimer's Disease (AD). The peptide Ala(N3)-KLVFF-NH2 was successfully designed and synthesized to target Aβ, with the aim of inhibiting its fibrillation and increase penetration ability by conjugating it to Mn Anderson-Evans molybdate, to potentially mitigate the development of Alzheimer's Disease (AD).